Photodynamic therapy (PDT) has been shown to be very effective in destroying diseased tissue and tumors using light that is absorbed by a photoreactive agent previously administered to a patient. The photoreactive agent is selectively preferentially absorbed by or linked to abnormal or diseased tissue and has a characteristic absorption waveband to which the waveband of the light administered to the patient corresponds. When activated by the light, the photoreactive agent produces compounds, such as singlet oxygen, that destroy the abnormal tissue.
While much of the earlier work in PDT has been directed to treating surface lesions, perhaps a much more important application is in destroying internal tumors within the body of a patient. PDT may be administered interstitially using light from an external laser that is coupled to a plurality of optical fibers. The optical fibers convey the light into a tumor mass within a patient's body; however, interstitial PDT has been used preclinically and clinically on only a very limited basis. The clinical application of interstitial PDT to oncology has been associated with several significant problems, including inadvertent damage to normal tissue, tumor regrowth, lack of efficacy, and surgical risk related to surgical emplacement of multiple optical fibers to assure adequate light delivery to relatively large tumor masses. The damage to normal tissue can occur during PDT and can be highly variable due to the non-homogeneous distribution of the photoreactive agent within a tumor and within normal tissue surrounding a tumor, and differences in the intensity and penetration depth of light into heterogeneous tumor tissue. Portions of a tumor may be destroyed, while other portions survive and remain viable, leading to tumor cell repopulation and regrowth of the tumor mass. Unintended destruction of normal tissue can have serious consequences, which is contrary to the intended goal of completely destroying the tumor, while sparing the normal tissue.
Monitoring tumor fluorescence has been suggested in the prior art as a possible way to determine the border of a tumor relative to normal tissue before beginning to administer PDT. However, there is no teaching in this prior art of monitoring the effect of PDT in real time to assess its progress in destroying diseased tissue nor any teaching of how to determine the effects of light distribution in a tumor. Other methods that have been proposed to monitor a tumor's condition include using radioactive-labeled agents to monitor blood flow in vessels supplying the tumor. These methods suffer from lack of repeatability, poor resolution at a boundary between a tumor and normal tissue, and inconvenient image capture. To implement such methods, it is typically necessary to transport a patient to specially fitted suites in which the imaging equipment is installed or to move relatively large imaging devices into the proximity of the patient. Also, toxicity due to repeated injection of radionuclides into a patient is a concern, since once an injected radionuclide is trapped within thrombosed and occluded vessels at the treatment site, there is no practical method to rapidly clear the trapped radionuclide material for another injection, in order to asses further vessel shut-down.
Thus, no practical method is disclosed in the prior art for real-time monitoring of interstitial PDT in order to assess the changing extent of tumor destruction and to avoid damage to surrounding normal tissue as the treatment progresses. Typically, since the photoreactive agent is administered to a patient as a bolus so that its concentration within the patient's body cannot thereafter be controllably varied other than by giving additional doses, the only available control in administering PDT is in regard to the light intensity, duration of light administered, the timing of light administered, and the total light dose administered to a treatment site. It would therefore be desirable to develop a technique for providing PDT that enables real-time monitoring of an internal treatment site, so that one or more of these parameters can be varied in response to changes in the treatment site as the PDT continues. Such a method would allow practical, cost-effective, and non-invasive determination of the effects of the PDT on a tumor at a treatment site and its progress in destroying the tumor, and would provide guidance in varying one or more of the parameters noted above to achieve a substantial clinical benefit at minimal risk to the patient.